Eur Radiol DOI 10.1007/s00330-014-3503-4
MAGNETIC RESONANCE
Magnetic resonance enterography for assessment of intestinal graft-versus-host disease after allogeneic stem cell transplantation Thorsten Derlin & Azien Laqmani & Simon Veldhoen & Ivayla Apostolova & Francis Ayuk & Gerhard Adam & Nicolaus Kröger & Peter Bannas
Received: 3 June 2014 / Revised: 10 November 2014 / Accepted: 13 November 2014 # European Society of Radiology 2014
Abstract Objectives To determine the diagnostic performance of MR enterography (MRE) for detection and grading of gastrointestinal graft-versus-host disease (GI GvHD) after hematopoietic stem cell transplantation (SCT). Methods Forty-one patients with known GvHD or suspected GvHD underwent MRE and GI endoscopy with multi-level biopsies. MRE images were reviewed for presence of intestinal wall inflammation. Clinical grading of GI GvHD was performed. Histopathological evaluation (HPE) served as the reference standard. Results Overall, MRE demonstrated a per-patient sensitivity of 81.5 % for detection of GI GvHD. The most common findings were intestinal wall thickening (81.5 % of GvHD patients), luminal stenosis (81.5 %), mural contrast enhancement (70.4 %), and ascites (59.3 %). These findings were also
T. Derlin (*) : A. Laqmani : S. Veldhoen : G. Adam : P. Bannas Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany e-mail: [email protected] T. Derlin Department of Nuclear Medicine, Hanover Medical School, Hanover, Germany S. Veldhoen Department of Diagnostic and Interventional Radiology, University Medical Center Würzburg, Würzburg, Germany I. Apostolova Department of Radiology and Nuclear Medicine, Otto-von-Guericke University, Magdeburg, Germany F. Ayuk : N. Kröger Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
observed in other conditions than GvHD. The most frequently involved intestinal segment was the sigmoid colon (63.0 %), followed by the ileum (59.3 %) and the jejeunum (51.9 %). The number of involved segments (rs =0.54, p =0.009) correlated significantly with clinical severity as determined by GvHD grading. Conclusions After allogeneic stem cell transplantation, MRE may (1) contribute to detection and localization of GI GvHD, and (2) add information indicating the clinical severity of disease, but findings are unspecific. False negative results may be observed not only in low-grade GI GvHD. Key Points • Magnetic resonance enterography (MRE) allows for detection of GI GvHD • Common findings are wall thickening, stenosis, mural contrast enhancement, and ascites • The extent of GI involvement on MRE correlates with clinical severity of GvHD • Involvement of sigmoid colon and small intestine is common • Findings are unspecific and also observed in other conditions, e.g. infectious enteritis Keywords MRI . Small bowel . Large bowel . Graft-versus-host-disease . Stem cell transplantation
Introduction Allogeneic stem cell transplantation (SCT) represents a potentially curative treatment approach for various hematological diseases, and is increasingly used [1–3]. The donor graft contains T lymphocytes which restore T cell-dependent immunity, assist hematopoietic engraftment and are crucial to inducing remission by contributing to the immunological graft-versus-tumour effect [4, 5]. However, they are also
Eur Radiol
responsible for graft-versus-host disease (GvHD) representing a major complication of hematopoietic stem cell transplantation [5, 6]. The frequency of GvHD depends on the conditioning regimen, the source of the hematopoietic stem cell graft, and the immunosuppressive treatment [7]. In patients with an HLA-compatible unrelated donor, GvHD may occur in 60 to 80 % of cases [8], and up to 60 % of patients with acute GvHD may develop gastrointestinal GvHD [9]. Intestinal GVHD is a progressive inflammatory process that can involve all sections of the gastrointestinal tract, but predominantly affects the terminal ileum and colon [10]. GvHD involves the epithelial surfaces of the mucous membranes and the crypts of the gastrointestinal tract, and consequently, histopathological evaluation may reveal flattening of surface epithelium, ulcerations, and apoptotic bodies at crypt bases [11]. Patients with intestinal GvHD may present with unspecific symptoms including nausea, vomiting, watery diarrhoea, intestinal bleeding, abdominal pain, and anorexia [10, 12]. GvHD represents a major contributing cause of treatment-related mortality [13, 14]. Acute gastrointestinal GvHD is currently usually diagnosed based on clinical symptoms and histopathological analyses of mucosal biopsy specimens obtained by endoscopy of the upper and lower intestinal tract [10]. However, both the endoscopic evaluation and the histology of the upper gut may completely miss patchy involvement and underestimate the severity of graft-versus-host disease elsewhere in the intestine [15]. Additionally, invasive diagnostic procedures including endoscopy with biopsies are associated with considerable health hazards in SCT patients with often poor overall performance status and frequent thrombocytopenia [16]. Magnetic resonance enterography (MRE) has been introduced as an alternative method to evaluate various intestinal pathologies including intestinal wall inflammation [17–19]. Particularly in Crohn’s disease, MRE has been demonstrated sensitively to identify active intestinal inflammation, to determine the extent and activity of disease, and reliably to reliably detect extraenteric complications [20–23]. Therefore, MRE may also represent a useful tool for evaluation of GI GvHD in order to determine the presence, the extent, and the severity of intestinal GvHD. Patients may have to undergo repeated imaging examinations to assess the status of their disease due to persisting or relapsing disease [12]. For all the reasons mentioned above, MRE, which lacks ionizing radiation, may be a suitable non-invasive diagnostic approach for identification of gastrointestinal GvHD after allogeneic SCT. There are limited data on the performance of imaging modalities in that clinical setting [24]. Therefore, the purpose of the present study was to determine the diagnostic performance of MRE for detection and grading of intestinal GvHD after allogeneic stem cell transplantation.
Materials and methods Study population The study group consisted of 41 patients (27 men, 14 women; mean age 54.0±31.3, range 19.8 – 71.5 years) who had been referred for evaluation of known or suspected gastrointestinal GvHD between April 2010 and May 2013. Subjects were selected according to the following inclusion and exclusion criteria: Inclusion: (I1) (I2) (I3) (I4)
image data digitally available for retrospective analysis, prior allogeneic stem cell transplantation, time interval between MRE and endoscopy
MAGNETIC RESONANCE
Magnetic resonance enterography for assessment of intestinal graft-versus-host disease after allogeneic stem cell transplantation Thorsten Derlin & Azien Laqmani & Simon Veldhoen & Ivayla Apostolova & Francis Ayuk & Gerhard Adam & Nicolaus Kröger & Peter Bannas
Received: 3 June 2014 / Revised: 10 November 2014 / Accepted: 13 November 2014 # European Society of Radiology 2014
Abstract Objectives To determine the diagnostic performance of MR enterography (MRE) for detection and grading of gastrointestinal graft-versus-host disease (GI GvHD) after hematopoietic stem cell transplantation (SCT). Methods Forty-one patients with known GvHD or suspected GvHD underwent MRE and GI endoscopy with multi-level biopsies. MRE images were reviewed for presence of intestinal wall inflammation. Clinical grading of GI GvHD was performed. Histopathological evaluation (HPE) served as the reference standard. Results Overall, MRE demonstrated a per-patient sensitivity of 81.5 % for detection of GI GvHD. The most common findings were intestinal wall thickening (81.5 % of GvHD patients), luminal stenosis (81.5 %), mural contrast enhancement (70.4 %), and ascites (59.3 %). These findings were also
T. Derlin (*) : A. Laqmani : S. Veldhoen : G. Adam : P. Bannas Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany e-mail: [email protected] T. Derlin Department of Nuclear Medicine, Hanover Medical School, Hanover, Germany S. Veldhoen Department of Diagnostic and Interventional Radiology, University Medical Center Würzburg, Würzburg, Germany I. Apostolova Department of Radiology and Nuclear Medicine, Otto-von-Guericke University, Magdeburg, Germany F. Ayuk : N. Kröger Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
observed in other conditions than GvHD. The most frequently involved intestinal segment was the sigmoid colon (63.0 %), followed by the ileum (59.3 %) and the jejeunum (51.9 %). The number of involved segments (rs =0.54, p =0.009) correlated significantly with clinical severity as determined by GvHD grading. Conclusions After allogeneic stem cell transplantation, MRE may (1) contribute to detection and localization of GI GvHD, and (2) add information indicating the clinical severity of disease, but findings are unspecific. False negative results may be observed not only in low-grade GI GvHD. Key Points • Magnetic resonance enterography (MRE) allows for detection of GI GvHD • Common findings are wall thickening, stenosis, mural contrast enhancement, and ascites • The extent of GI involvement on MRE correlates with clinical severity of GvHD • Involvement of sigmoid colon and small intestine is common • Findings are unspecific and also observed in other conditions, e.g. infectious enteritis Keywords MRI . Small bowel . Large bowel . Graft-versus-host-disease . Stem cell transplantation
Introduction Allogeneic stem cell transplantation (SCT) represents a potentially curative treatment approach for various hematological diseases, and is increasingly used [1–3]. The donor graft contains T lymphocytes which restore T cell-dependent immunity, assist hematopoietic engraftment and are crucial to inducing remission by contributing to the immunological graft-versus-tumour effect [4, 5]. However, they are also
Eur Radiol
responsible for graft-versus-host disease (GvHD) representing a major complication of hematopoietic stem cell transplantation [5, 6]. The frequency of GvHD depends on the conditioning regimen, the source of the hematopoietic stem cell graft, and the immunosuppressive treatment [7]. In patients with an HLA-compatible unrelated donor, GvHD may occur in 60 to 80 % of cases [8], and up to 60 % of patients with acute GvHD may develop gastrointestinal GvHD [9]. Intestinal GVHD is a progressive inflammatory process that can involve all sections of the gastrointestinal tract, but predominantly affects the terminal ileum and colon [10]. GvHD involves the epithelial surfaces of the mucous membranes and the crypts of the gastrointestinal tract, and consequently, histopathological evaluation may reveal flattening of surface epithelium, ulcerations, and apoptotic bodies at crypt bases [11]. Patients with intestinal GvHD may present with unspecific symptoms including nausea, vomiting, watery diarrhoea, intestinal bleeding, abdominal pain, and anorexia [10, 12]. GvHD represents a major contributing cause of treatment-related mortality [13, 14]. Acute gastrointestinal GvHD is currently usually diagnosed based on clinical symptoms and histopathological analyses of mucosal biopsy specimens obtained by endoscopy of the upper and lower intestinal tract [10]. However, both the endoscopic evaluation and the histology of the upper gut may completely miss patchy involvement and underestimate the severity of graft-versus-host disease elsewhere in the intestine [15]. Additionally, invasive diagnostic procedures including endoscopy with biopsies are associated with considerable health hazards in SCT patients with often poor overall performance status and frequent thrombocytopenia [16]. Magnetic resonance enterography (MRE) has been introduced as an alternative method to evaluate various intestinal pathologies including intestinal wall inflammation [17–19]. Particularly in Crohn’s disease, MRE has been demonstrated sensitively to identify active intestinal inflammation, to determine the extent and activity of disease, and reliably to reliably detect extraenteric complications [20–23]. Therefore, MRE may also represent a useful tool for evaluation of GI GvHD in order to determine the presence, the extent, and the severity of intestinal GvHD. Patients may have to undergo repeated imaging examinations to assess the status of their disease due to persisting or relapsing disease [12]. For all the reasons mentioned above, MRE, which lacks ionizing radiation, may be a suitable non-invasive diagnostic approach for identification of gastrointestinal GvHD after allogeneic SCT. There are limited data on the performance of imaging modalities in that clinical setting [24]. Therefore, the purpose of the present study was to determine the diagnostic performance of MRE for detection and grading of intestinal GvHD after allogeneic stem cell transplantation.
Materials and methods Study population The study group consisted of 41 patients (27 men, 14 women; mean age 54.0±31.3, range 19.8 – 71.5 years) who had been referred for evaluation of known or suspected gastrointestinal GvHD between April 2010 and May 2013. Subjects were selected according to the following inclusion and exclusion criteria: Inclusion: (I1) (I2) (I3) (I4)
image data digitally available for retrospective analysis, prior allogeneic stem cell transplantation, time interval between MRE and endoscopy
